cells and monocytes especially during relapses. This phenotype is associated with a decreased basal secretion of IL-6 and TNF-a by B cells of RR-MS, and of IL-1a and IL-1b by monocytes of SP and PP-MS patients. Upon stimulation, there is a rescue of the level of these cytokines, which reach similar levels in all conditions tested. These data clearly suggest that there is a dysregulated innate immune response in MS, but with different profiles depending on the stage of the disease. doi:10.1016/j.jneuroim.2014.08.237 309 Cell differentiation modulates intracellular antiviral responses in neuronal cells Tomoh Matsumiya, Ryo Hayakari, Fei Xing, Hidemi Yoshida, Tadaatsu Imaizumi Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan Pattern recognition receptors (PRRs) are receptors expressed by cells from the innate immune system acting as sensors to detect rapidly invading pathogens. Subsets of the PRRs trigger the activation of intracellular signaling pathways, leading to the activation of a series of antimicrobial innate immune responses. The repertoire of such signal transducing-type PRRs includes membrane-bound Toll-like receptors (TLRs) as well as cytosolic receptors such as RNA helicase retinoic acid-inducible gene-I (RIG- I)-like receptors (RLRs) and Nod-like receptors (NLRs). In most types of cells, the RLR family serves as a cytoplasmic sensor for viral RNA. The RLR family is composed of three members, RIG-I, melanoma differentiation-associated gene-5 (MDA-5) and laboratory of genet- ics and physiology 2 (LPG2). Accumulating evidences indicate that RLRs can distinguish among different RNA ligands. MDA-5 prefers to recognize Picornaviridae family while RIG-I recognizes most of the RNA virus, suggesting that RIG-I is the essential molecule among the RLRs. The central nervous system (CNS) has long been considered as an immune-privileged site since the blood–brain barrier (BBB) was being investigated. However, recent studies have shown that the immune responses are observed in the CNS during microbial infections. Microglia are considered to function as macrophages in the CNS. In addition, astrocytes are shown to be important regulators of innate inflammation in response to viral infection in the CNS. On the other hand, little evidence has shown a role of neuronal cells in innate immune reactions. This study explored if neuronal cells can exert RIG-I-mediated antiviral innate immune responses. We initially found that undifferentiated PC-12 cells expressed interferon (IFN)- beta, a representative type I IFN, in response to nerve growth factor (NGF). The NGF-induced IFN-beta expression was enhanced in NGF- differentiated PC-12 cells, indicating that neuronal differentiation is important to the expression of IFN-beta that is crucial molecule in antiviral innate immunity. NGF altered the expression level of RIG-I in neither undifferentiated nor NGF-differentiated PC-12 cells. Synthetic double-stranded RNA induced the expression of RIG-I in the undifferentiated cells, and again the expression of RIG-I was enhanced in the NGF-differentiated cells. We conclude that neuronal cells potentially have antiviral properties and may contribute, at least partially, to antiviral host defense in brain. doi:10.1016/j.jneuroim.2014.08.238 248 The severity of the clinical course in EAE mice is related to myeloid-derived suppressor cell enrichment in both the spleen and the spinal cord Carolina Melero- jerez, Fernando De Castro, Diego Clemente Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Toledo, Spain The Relapsing–Remitting (RR) is the most frequent clinical variant of multiple sclerosis (MS), with phases of increasing neurological symptoms (relapses) and periods of partial recovery (remissions). This implies the existence of cellular immunomodulatory mechanisms triggering the relapsing-to-remitting transition. Myeloid-derived sup- pressor cells (Arg-I + CD11b + Gr-1 + -MDSCs) have been described to transiently enter the spinal cord of EAE mice in parallel to the clinical signs, and control the immune response by accelerating T cell apoptosis. Besides, their differentiation, and thus the reduction of their immunosuppressor activity, contributes to the delay in the recovery of the EAE symptoms. However, the relation between the MDSC density and the aggressiveness of the EAE clinical course remains unexplored. Our data indicate that the EAE mice evolve with different aggressiveness in their clinical courses. In the present study, we confirm a significant inverse correlation between the splenic content of MDSCs and several clinical data. Moreover, animals suffering from a mild clinical course showed lesser demyelination than those suffering from a severe EAE. Furthermore, the expression pattern of the Arg-I + /CD11b + /Gr-1 + -cells was also different attending to the severity of the clinical evolution: i) mild EAE mice showed more defined infiltrated areas in their spinal cords, mainly located in the periphery of the white matter and always associated to demyelinated areas; ii) mice suffering from severe EAE clinical course presented a larger number of Arg-I + -cells than mild ones, which could be detected also in the grey matter; iii) in the spinal cord, mice with a moderate disease present a much higher density of Arg-I + CD11b + Gr-1 + -MDSCs than those suffering from a severe EAE. In addition, we have analysed the relationship between the aggressiveness of the EAE clinical course and oligodendrocyte precursor cell biology. In sum, our present findings add new insights about the putative use of this cell type as biomarker for a better diagnosis and prognosis on MS severity. This work was supported by the Spanish Ministerio de Economía y Competitividad (MINECO; SAF2012-40023; RD07-0060-2007 and RD12-0032/0012, and partially cofinanced by FEDER, European Union, “Una manera de hacer Europa”) to FdC and ARSEP Foundation to DC. DC and FdC are hired by SESCAM. CM-J holds a fellowship by the Spanish MINECO (BES-2013-062630). doi:10.1016/j.jneuroim.2014.08.239 585 Sirtuin-1 is involved in lipopolysaccharide- and interferon beta-mediated interleukin-10 regulation in human monocytes Yusei Miyazaki a , Masaaki Niino a , Toshiyuki Fukazawa b , Eri Takahashi a , Takayuki Nonaka c , Ryutaro Ochi c , Naoya Minami c , Naoto Fujiki c , Shizuki Doi c , Seiji Kikuchi c a Clinical Research, Hokkaido Medical Center, Sapporo, Japan; b Neurology, Sapporo Neurology Clinic, Sapporo, Japan; c Neurology, Hokkaido Medical Center, Sapporo, Japan Abstracts 89